New insecticides with novel modes of action are urgently needed to improve public health in many countries around the world. This project addresses several important questions regarding nutrient transport and signaling pathways in the fat body of the yellow fever mosquito, Aedes aegypti. We will characterize the mode of action of two essential mosquito cationic amino acid transporters and test and improve promising compounds to inhibit cationic amino acid transport. We will complement these approaches with the development of an in silico mosquito fat body gene knowledge network designed to identify genes in the amino acid signaling and transport cascades downstream of cationic amino acid transporters. The proposed work will prove significant for human health through the significant gain of knowledge on amino acid transport and signaling in mosquitoes. Amino acid transport inhibitors have the potential to give rise to a new generation of public health insecticides. In addition, this study will expand our knowledge of the functional mechanism of cationic amino acid transporter in insects with implications for understanding essential amino acid transporters in humans and other model systems.